Burkholderia cepacia complex (Bcc) is a group of 17 species of Gram negative bacteria [1-3], two of which, B. multivorans and B. cenocepacia, are particularly virulent [4]. Bcc is reported to cause infections in 3.5% of CF patients in the world, which is significant, as CF patients colonised with Bcc experience a more rapid decline than those colonised with the more commonly acquired pathogen, P. aeruginosa [5]. Once a patient is colonised with Bcc, it is rarely eradicated due to the resistance of Bcc to antibiotics [6] and its inherent resistance to antimicrobial peptides [7, 8]. Strict segregation measures have limited patient-to-patient spread [9] and the majority of acquisitions are from the environment with B. multivorans being most frequently acquired; therefore Bcc still represents a substantial threat to CF patients. Furthermore, Bcc contamination of pharmaceutical formulations, medical devices and disinfectants has led to number of recent outbreaks among both CF and non-CF populations. [3, 10]. Furthermore, Bcc is an emerging pathogen in nosocomial infections among chemotherapy patients and other immunosuppressed individuals [11, 12].
Bcc is unique among CF pathogens in that it invades the lung epithelium and escapes beyond the lung. Previous work by the Applicant has shown that Bcc attaches laterally to the surfaces of epithelial cells, prior to invasion inside the cells [13].
There have been only two in vivo mouse vaccination studies reported against Bcc, both of which involved unpurified OMP preparations. Bertot et al. described the protection of mice against either B. cenocepacia or B. multivorans challenge following nasal immunisation of mice with an enriched OMP preparation administered with the mucosal adjuvant adamantylamide dipeptide [14]. More recently mice were protected from B. cenocepacia using enriched OMPs which were administered intranasally as a nanoemulsion preparation [15]. Both studies demonstrate the potential for OMPs as protective antigens, but were carried out with unpurified OMP preparations, which are ill-defined, rather than pure specific identified specific antigens. A 17 kDa OMP was identified as an immunodominant antigen in the latter study [15].
In addition, two related organisms, Burkholderia pseudomallei and Burkholderia mallei are also members of this genus. Burkholderia pseudomallei, the causative agent of melioidosis, is a Gram-negative, intracellular pathogen endemic in Southeast Asia and Northern Australia. The disease is considerably variable in humans ranging from acute septicaemia, pneumonia to chronic or latent infection which can persist and emerge decades later. It has recently been identified in the CF and CGD population also. The bacterium is intrinsically antibiotic resistant and has a mortality rate up to 50%; however despite its significant morbidity and mortality, there is currently no licensed vaccine against this infection. B. mallei is an obligate pathogen which causes glanders in horses. It is highly infectious in humans by aerosol route there have been concerns it may be used as means of biological warfare. No effective vaccines or therapeutics of either melioidosis or glanders currently exist
It is an object of the invention to overcome at least one of the above-referenced problems.